The Biological Actions and Mechanisms of Brain-Derived Neurotrophic Factor in Healthy and Disordered Brains

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits neuronal survival and differentiation, synaptic transmission, and the modulation of synaptic plasticity. The biological actions of BDNF are mediated via two distinct receptors: the high-affinity tropomyosin-related kinase B (TrkB) receptor and the low-affinity p75 neurotrophin receptor (p75NTR). Recent findings regarding the actions and mechanisms of BDNF are reviewed here. Activity-dependent synaptic plasticity, as exemplified by long-term potentiation (LTP) and long-term depression (LTD), underlies the cellular mechanism of learning and memory. An accumulating body of evidence shows that BDNF modulates synaptic plasticity. This function requires extracellular neurotrophin release, synaptic activity-dependent local protein synthesis. In addition, a precursor of BDNF, proBDNF, is emerging as a new ligand with biological activities that are distinct from those of BDNF. The proteolytic cleavage of proBDNF is also proposed as a mechanism that determines the direction of BDNF actions. This review discusses the post-translational processing of proBDNF, the modulatory roles of the human BDNF polymorphism Val66Met, recent reports of the novel mechanisms of BDNF expression, and clinical reports showing the roles of BDNF in the blood. Taken together, these data provide new insights into the biological roles of BDNF and its related molecules in the central nervous system.

Fluorescence imaging of drug target proteins using chemical probes

Fluorescence imaging can provide valuable information on the expression,distribution,and activity of drug target proteins.Chemical probes are useful small-molecule tools for fluorescence imaging with high structural flexibility and biocompatibility.In this review,we briefly introduce two classes of fluorescent probes for the visualization of drug target proteins.Enzymatically activatable probes make use of the specific enzymatic transformations that generally produce a fluorogenic response upon reacting with target enzymes.Alternatively,specific imaging can be conferred with a ligand that drives the probes to target proteins,where the labeling relies on noncovalent binding,covalent inhibition,or traceless labeling by ligand-directed chemistry.

Controlled synthesis of Ce(OH)CO_3 flowers by a hydrothermal method and their thermal conversion to CeO_2 flowers

Highly uniform Ce（OH）CO3 flowers were successfully prepared in large quantities using a facile hydrothermal approach from the reaction of Ce（NH4）（NO3）4 with CO（NH2）2 at 160℃ in a water-N2H4 complex. The influences of the N2H4 content and temperature on flower formation were discussed. CeO2 flowers were prepared by thermal conversion of Ce（OH）CO3 flowers at 500 ℃ in air. Both Ce（OH）CO3 and CeO2 flowers were characterized by X-ray powder diffraction （XRD）, and scanning electron microscopy （SEM）. The UV-vis adsorption spectrum of the CeO2 flowers showed that the band gap energy （Eg） is 2.66 eV, which is lower than that of bulk ceria.

Temperature-dependent phonon spectra of magnetic random solid solutions

A first-principles-based computational tool for simulating phonons of magnetic random solid solutions including thermal magnetic fluctuations is developed.The method takes fluctuations of force constants due to magnetic excitations as well as due to chemical disorder into account.The developed approach correctly predicts the experimentally observed unusual phonon hardening of a transverse acoustic mode in Fe–Pd an Fe–Pt Invar alloys with increasing temperature.This peculiar behavior,which cannot be explained within a conventional harmonic picture,turns out to be a consequence of thermal magnetic fluctuations.The proposed methodology can be straightforwardly applied to a wide range of materials to reveal new insights into physical behaviors and to design materials through computation,which were not accessible so far.

Molecule/Semiconductor Hybrid Materials for Visible-Light CO_(2) Reduction:Design Principles and Interfacial Engineering

CONSPECTUS:Because of increasing concerns over the depletion of energy sources and the concomitant increase in CO_(2)emissions,much attention has been devoted to carbon capture and utilization technologies.Among the various methods and schemes proposed,visible-light-driven CO_(2)reduction in combination with water oxidation,one of the representative models of artificial photosynthesis,is an attractive solution because it enables abundant water and inexhaustible solar energy to be used to produce value-added chemicals.Molecular metal complexes and semiconductors are promising candidates for photocatalysts that can reduce CO_(2)to CO,formate,formaldehyde,or other hydrocarbons.Although both molecular metal complexes and semiconductors have strengths and weaknesses,their weaknesses(low oxidation ability and low selectivity for reduction reactions)can be overcome via the construction of a suitable molecule/semiconductor hybrid material.However,facilitating electron transfer at the molecule/semiconductor junction while suppressing unfavorable back electron transfer events is challenging.Consequently,the number of molecule/semiconductor hybrid systems that show a reasonable level of visible-light photocatalytic activity is limited,despite the development of a large number of visible-light-driven semiconductors and molecular photocatalysts(or catalysts).In this Account,we describe our approaches to developing hybrid photocatalysts and photoelectrodes for CO_(2)reduction.We have been developing both molecular(photo)catalysts and semiconductor photocatalysts individually,the latter of which are also designed for visible-light water splitting.For example,supramolecular photocatalysts that possess both photosensitizer and catalyst units in a single molecule can reduce CO_(2)to formate or CO in a homogeneous system,with high selectivity toward the desired product and high quantum yields of several tens of percent.However,nonoxide semiconductors such as C/N-based polymers and mixed-anion compounds exhibit a strong photooxidation ability under visible light.Carefully designed molecule/semiconductor hybrid materials achieve CO_(2)reduction under visible light with high product selectivity and stability even in an aqueous environment,where the concentration of CO_(2)is low but that of protons is high.Visible-light CO_(2)reduction combined with H2O oxidation is possible via the construction of a photoelectrochemical cell that comprises a molecular photocathode and an n-type semiconductor photoanode.Although our photosystems can be regarded as model systems for artificial photosynthesis,their light-energy conversion efficiencies are still unsatisfactory.To improve the efficiency,materials design,including interfacial engineering at the molecule/semiconductor junction,is important and is the general theme of the results highlighted in this Account.

Nanofluidics for sub-single cellular studies:Nascent progress,critical technologies,and future perspectives

In the field of cell studies,there is a burgeoning trend to further downscale the investigation from a single-cell level to a sub-single-cell level.Subcellular matter is the basic content in cells and correlates with cell heterogeneity.Sub-single cellular studies focus on the subcellular matter in single cells and aim to understand the details and heterogeneity of individual cells in terms of the subcellular matter or even at the single component/vesicle/molecule level.Hence,sub-single cellular studies can provide deeper insights into fundamental cell biology and the development of new diagnostic and therapeutic technologies and applications.Nonetheless,the contents of a single cell are not only ultra-small in volume but also extremely complex in composition,far exceeding the capabilities of most tools used in current cell studies.We believe that nanofluidics holds great potential in providing ideal tools for sub-single cellular studies,not only because of their capability to handle femtoliter/attoliter-scale samples,but also because of their possibility to manipulate and analyze subcellular matters at the single component/vesicle/molecule level in a high-throughput manner.In this review,we summarize the efforts in the field of nanofluidics for sub-single cellular studies,focusing on nascent progress and critical technologies that have the potential to overcome the technical bottlenecks.Some challenges and future opportunities to integrate with information sciences are also discussed.

Application of a Nanostructured Composite Material Constructed by Self-Assembly of Titanoniobate Nanosheets and Cobalt Porphyrin to Electrocatalytic Reduction of Oxygen

A novel layered nanocomposite was fabricated by the self-assembly of TiNbOs-nanosheets and 5,10,15,20- tetrakis（N-methylpyridinium-4-yl）porphyrinatocobalt（III） （CoTMPyP）. The product was characterized by a variety of analytical techniques such as XRD, EDX, Zeta potential, AFM, UV-vis, IR and SEM, the guest species were intercalated into the interlayer gallery of KTiNbO5 successfully. The electrochemical property of TiNbO5-CoTMPyP as an electrode modifying material was examined by cyclic voltammetry test in PBS solution （pH = 7）, and the hybrid exhibited excellent electrocatalytical property towards oxygen reduction with the peak potential shifting from -0.703 V （bare GCE） to -0.278 V （modified electrode）. The result also indicated that the oxygen molecule was reduced to H2O2 by a two-electron process.

ATP binding cassette proteins ABCG37 and ABCG33 function as potassium-independent cesium uptake carriers in Arabidopsis roots

Radiocesium accumulated in the soil by nuclear accidents is a major environmental concern.The transport process of cesium(Cs^(+))is tightly linked to the indispensable plant nutrient potassium(K^(+))as they both belong to the group I alkali metals with similar chemical properties.Most of the transporters that had been characterized to date as Cs*transporters are directly or indirectly linked to K^(+).Using a combinatorial approach of physiology,genetics,cell biology,and root uptake assay,here we identified two ATP-binding cassette(ABC)proteins,ABCG37 and ABCG33,as facilitators of Cs^(+)influx.A gain-of-function mutant of ABCG37(abcg37-1)showed increased sensitivity to Cs^(+)-induced root growth inhibition,while the double knockout mutant of ABCG33 and ABCG37(abcg33-1abcg37-2)showed resistance,whereas the single loss-of-function mutants of ABCG33 and ABCG37 did not show any alteration in Cs^(+)response.In planta short-term radioactive Cs^(+)-uptake assay along with growth and uptake assays in a heterologous system confirmed ABCG33 and ABCG37 as Cs^(+)-uptake carriers.Potassium response and content were unaffected in the double-mutant background and yeast cells lacking potassium-uptake carriers transformed with ABCG33 and ABCG37 failed to grow in the absence of K^(+),confirming that Cs^(+)uptake by ABCG33 and ABCG37 is independent of K^(+).Collectively,this work identified two ABC proteins as new Cs^(+)-influx carriers that act redundantly and independent of the K^(+)-uptake pathway.

Direct Simulation Methods for Scalar-Wave Envelopes in Two-Dimensional Layered Random Media Based on the Small-Angle Scattering Approximation

This study presents stochastic methods to simulate wave envelopes in layeredrandom media. High-frequency Seismograms of small earthquakes are so complexdue to lithospheric inhomogeneity that seismologists often analyze wave envelopesrather than wave traces to quantify the subsurface inhomogeneity. Since thestatistical properties of the inhomogeneity vary regionally, it is important to developand examine direct envelope simulation methods for non-uniform random media. Asa simple example, this study supposes planewave propagation through two-layer randommedia in 2-D composed of weak and strong inhomogeneity zones. The characteristicspatial-scale of the inhomogeneity is supposed to be larger than the wavelength,where small-angle scattering around the forward direction dominates large-angle scattering.Two envelope simulation methods based on the small-angle scattering approximationare examined. One method is to solve a differential equation for the twofrequencymutual coherence function with the Markov approximation. The other isto solve the stochastic ray bending process by using the Monte Carlo method basedon the Markov approximation for the mutual coherence function. The resultant waveenvelopes of the two methods showed excellent coincidence both for uniform and fortwo-layer random media. Furthermore, we confirmed the validity of the two methodscomparing with the envelopes made from the finite difference simulations of waves.The two direct envelope simulation methods presented in this study can be a mathematicalbase for the study of high-frequency wave propagation through randomlyinhomogeneous lithosphere in seismology.

Shedding new light on the dislocation-mediated plasticity in wurtzite ZnO single crystals by photoindentation

Dislocation-mediated plasticity in inorganic semiconductors and oxides has attracted increasing research interest because of the promising mechanical and functional properties tuned by dislocations.In this study,we investigated the effects of light illumination on the dislocation-mediated plasticity in hexagonal wurtzite ZnO,a representative third-generation semiconductor material.A(0001)45o off sample was specially designed to preferentially activate the basal slip on(0001)plane.Three types of nanoindentation tests were performed under four different light conditions(550 nm,334 nm,405 nm,and darkness),including low-load(60μN)pop-in tests,high-load(500μN)nanoindentation tests,and nanoindentation creep tests.The maximum shear stresses at pop-in were found to approximate the theoretical shear strength regardless of the light conditions.The activation volume at pop-ins was calculated to be larger in light than in darkness.Cross-sectional transmission electron microscope images taken from beneath the indentation imprints showed that all indentation-induced dislocations were located beneath the indentation imprint in a thin-plate shape along one basal slip plane.These indentation-induced dislocations could spread much deeper in darkness than in light,revealing the suppressive effect of light on dislocation behavior.An analytical model was adopted to estimate the elastoplastic stress field beneath the indenter.It was found that dislocation glide ceased at a higher stress level in light,indicating the increase in the Peierls barrier under light illumination.Furthermore,nanoindentation creep tests showed the suppression of both indentation depth and creep rate by light.Nanoindentation creep also yielded a larger activation volume in light than in darkness.

Fabrication of luminescent patterns using aggregation-induced emission molecules by an electrolytic micelle disruption approach

Herein,we report an electrochemical strategy that could control the location of aggregation-induced emission(AIE)molecules on patterned electrodes in a precise and facile way,producing photoluminescent and electrochemiluminescent patterns with a variety of colors.A micelle composed of electroactive surfactants was broken during the electrooxidation process,in which AIE molecules inside these micelles were released on patterned electrodes.These patterned electrodes were pretreated by not only metal,but also multifarious conducting polymers(CPs).An in-depth investigation clarified a correlation between the variety of CPs used as electrodes and the oxidation rate of the electroactive surfactant due to different catalytic performances of CPs.Furthermore,combined with wireless and gradient features of bipolar electrochemistry,a gradient luminescent pattern was easily achieved.The current studies suggest more abundant luminescent patterns using AIE luminophores can be developed by such an electrochemical method,in both of graphical shapes and emitting colors.

Improvement in growth yield of single-walled carbon nanotubes with narrow chirality distribution by pulse plasma CVD

A pulse plasma chemical vapor deposition (CVD) technique was developed for improving the growth yield of single-walled carbon nanotubes (SWNTs) with a narrow chirality distribution. The growth yield of the SWNTs could be improved by repetitive short duration pulse plasma CVD, while maintaining the initial narrow chirality distribution. Detailed growth dynamics is discussed based on a systematic investigation by changing the pulse parameters. The growth of SWNTs with a narrow chirality distribution could be controlled by the difference in the nucleation time required using catalysts comprising relatively small or large particles as the key factor. The nucleation can be controlled by adjusting the pulse on/ofF time ratio and the total processing time.

Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma

Uterine tumors are the most common type of gynecologic neoplasm.Uterine leiomyosarcoma(LMS)is rare,accounting for 2%to 5%of tumors of the uterine body.Uterine LMS develops more often in the muscle tissue layer of the uterine body than in the uterine cervix.The development of gynecologic tumors is often correlated with female hormone secretion;however,the development of uterine LMS is not substantially correlated with hormonal conditions,and the risk factors are not yet known.Radiographic evaluation combined with PET/CT can be useless in the diagnosis and surveillance of uterine LMS.Importantly,a diagnostic biomarker,which distinguishes malignant LMS and benign tumor leiomyoma(LMA)is yet to be established.Accordingly,it is necessary to analyze risk factors associated with uterine LMS in order to establish a method of treatment.LMP2-deficient mice spontaneously develop uterine LMS,with a disease prevalence of~40%by 14 months of age.It is therefore of interest whether human uterine LMS shows a loss of LMP2 expression.We found LMP2 expression is absent in human LMS,but present in human LMA.Therefore,defective LMP2 expression may be one of the risk factors for LMS.LMP2 is potentially a diagnostic biomarker for uterine LMS,and gene therapy with LMP2-encording DNA may be a new therapeutic approach.

Deep-learning-based quality filtering of mechanically exfoliated 2D crystals

Two-dimensional(2D)crystals are attracting growing interest in various research fields such as engineering,physics,chemistry,pharmacy,and biology owing to their low dimensionality and dramatic change of properties compared to the bulk counter parts.Among the various techniques used to manufacture 2D crystals,mechanical exfoliation has been essential to practical applications and fundamental research.However,mechanically exfoliated crystals on substrates contain relatively thick flakes that must be found and removed manually,limiting high-throughput manufacturing of atomic 2D crystals and van der Waals heterostructures.Here,we present a deep-learning-based method to segment and identify the thickness of atomic layer flakes from optical microscopy images.Through carefully designing a neural network based on U-Net,we found that our neural network based on Unet trained only with the data based on realistically small number of images successfully distinguish monolayer and bilayer MoS2 and graphene with a success rate of 70–80%,which is a practical value in the first screening process for choosing monolayer and bilayer flakes of all flakes on substrates without human eye.The remarkable results highlight the possibility that a large fraction of manual laboratory work can be replaced by AI-based systems,boosting productivity.

Charge generation in organic solar cells: Journey toward 20% power conversion efficiency

The power conversion efficiencies of organic solar cells(OSCs)have routinely lagged far behind those of their inorganic counterparts.However,owing to the enor-mous contributions of many researchers,the power conversion efficiencies of OSCs have rapidly improved and now exceed 19%.The charge generation mechanisms in OSCs have been heavily debated during this period while acquiring valuable knowl-edge.This review highlights fundamental and cutting-edge research that rationalizes why OSCs can generate photocurrent so efficiently.In particular,a photophysi-cist’s views on exciton diffusion to donor:acceptor interfaces,charge transfer at the donor:acceptor interface,and long-range spatial dissociation of charge transfer states are discussed.Although a general consensus in this area has not been reached yet,recent time-resolved spectroscopic measurements provide important photophys-ical insights that can help achieving a better understanding of the charge generation mechanism in OSCs.Based on these observations,future research directions for realizing further improvements in OSC performance are discussed.

Effects of catalyst loading amount on the synthesis of poly（3-hexylthiophene） via externally initiated Kumada catalyst-transfer polycondensation

A series of model polymerization are carried out via the one-pot externally initiated Kumada catalyst-transfer polycondensation （KCTP） of 2-bromo-5-chloromagne- slum thiophene monomers, and the excess amount of initiators or catalysts are found no need to be isolated during the polycondensation process. Especially, the impacts of the nickel catalyst loading variation on regioregularity （rr）, yield, molecular weight （Mn）, polydispersity （PDI） and initiation efficiency of poly（3-hexylthiophene） （P3HT） are systematically investigated. The IH NMR, size-exclusion chromatography （SEC）, and MALDI-TOF mass spectroscopy results indicated that an excess amount of catalyst does not influence yield, rr, Mn, and PDI of P3HT, nor the initiation efficiency. However, the PDI of the product is broad, and the Mn and rr values decreased in the absence of 1,3-bis （diphenylphosphino）propane （dppp）. It can be concluded that the in-situ KCTP polymerization of P3HT is a practical and effective process. These results are especially valuable for the synthesis of all-conjugated block copolymers where macroinitiators are used.

Fabrication of cellulose based superhydrophobic microspheres for the production of magnetically actuatable smart liquid marbles

Cellulose microspheres were fabricated on the basis of sol-gel transition using NaOH/urea/H_(2)O as the solvent system.These microspheres had an average diameter of about 30μm.Upon modification with Fe_(3)O_(4) and poly(DOPAm-co-PFOEA),superhydrophobic magnetic cellulose microspheres were generated,which were analyzed by FTIR,TG,XRD,XPS and water contact angle tests.Magnetic cellulose microspheres contained approximately 15 wt%of Fe_(3)O_(4).Poly(DOPAm-co-PFOEA)/Fe_(3)O_(4)/cellulose microspheres and had a low surface energy and a high water-repellency.These superhydrophobic microspheres were also converted into liquid marbles via an easily scalable process.